{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:51:36Z","timestamp":1788580296842,"version":"build-2803163510"},"reference-count":22,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg\/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the <jats:italic>Douleur Neuropathique<\/jats:italic> 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg\/day) in a randomized sequence so that comparisons could be made within participants and between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03928093\">NCT03928093<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamadermatol.2024.3767","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T15:31:51Z","timestamp":1729697511000},"page":"1314","source":"Crossref","is-referenced-by-count":5,"title":["Pregabalin for Neuropathic Pain and Itch in Recessive Dystrophic Epidermolysis Bullosa"],"prefix":"10.1001","volume":"160","author":[{"given":"Margarita","family":"Calvo","sequence":"first","affiliation":[{"name":"Physiology Department, Biological Sciences Faculty, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"},{"name":"Millennium Nucleus for the Study of Pain, Santiago, Chile"},{"name":"Anesthesiology Division, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Tejos-Bravo","sequence":"additional","affiliation":[{"name":"Physiology Department, Biological Sciences Faculty, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"},{"name":"Millennium Nucleus for the Study of Pain, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Passi-Solar","sequence":"additional","affiliation":[{"name":"Public Health Department, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Physiology Department, Biological Sciences Faculty, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"},{"name":"Millennium Nucleus for the Study of Pain, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacia","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Center for Genetics and Genomics, Faculty of Medicine, Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago, Chile"},{"name":"Fundaci\u00f3n DEBRA Chile, Santiago, Chile"},{"name":"Department of Cellular and Molecular Biology, Biological Sciences Faculty, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Lara-Corrales","sequence":"additional","affiliation":[{"name":"Division of Dermatology, The Hospital for Sick Children, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pope","sequence":"additional","affiliation":[{"name":"Division of Dermatology, The Hospital for Sick Children, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"6","key":"doi240045r1","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.jaad.2014.01.903","article-title":"Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification.","volume":"70","author":"Fine","year":"2014","journal-title":"J Am Acad Dermatol"},{"issue":"2","key":"doi240045r2","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/pde.13392","article-title":"A comprehensive next-generation sequencing assay for the diagnosis of epidermolysis bullosa.","volume":"35","author":"Lucky","year":"2018","journal-title":"Pediatr Dermatol"},{"issue":"1","key":"doi240045r3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s13023-021-01811-7","article-title":"A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa.","volume":"16","author":"Tang","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"doi240045r4","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12916-014-0178-2","article-title":"Pain care for patients with epidermolysis bullosa: best care practice guidelines.","volume":"12","author":"Goldschneider","year":"2014","journal-title":"BMC Med"},{"issue":"5","key":"doi240045r5","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1093\/brain\/awx069","article-title":"Recessive dystrophic epidermolysis bullosa results in painful small fibre neuropathy.","volume":"140","author":"von Bischhoffshausen","year":"2017","journal-title":"Brain"},{"issue":"1","key":"doi240045r6","doi-asserted-by":"publisher","first-page":"6","DOI":"10.5021\/ad.2016.28.1.6","article-title":"Quality of Life and economic burden in recessive dystrophic epidermolysis bullosa.","volume":"28","author":"Jeon","year":"2016","journal-title":"Ann Dermatol"},{"issue":"4","key":"doi240045r7","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/s10880-010-9205-4","article-title":"Psychiatric symptoms and quality of life in patients affected by epidermolysis bullosa.","volume":"17","author":"Margari","year":"2010","journal-title":"J Clin Psychol Med Settings"},{"issue":"3","key":"doi240045r8","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.4065\/mcp.2009.0649","article-title":"Recommendations for the pharmacological management of neuropathic pain: an overview and literature update.","volume":"85","author":"Dworkin","year":"2010","journal-title":"Mayo Clin Proc"},{"issue":"8","key":"doi240045r9","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1136\/adc.2004.068775","article-title":"Lethal cardiomyopathy in epidermolysis bullosa associated with amitriptyline.","volume":"90","author":"Taibjee","year":"2005","journal-title":"Arch Dis Child"},{"key":"doi240045r10","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/1745-0179-4-18","article-title":"Duloxetine and suicide attempts: a possible relation.","volume":"4","author":"Salem","year":"2008","journal-title":"Clin Pract Epidemiol Ment Health"},{"key":"doi240045r11","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3389\/fphar.2011.00028","article-title":"Alpha 2 Delta (a(2)d) ligands, gabapentin and pregabalin: what is the evidence for potential use of these ligands in irritable bowel syndrome.","volume":"2","author":"Gale","year":"2011","journal-title":"Front Pharmacol"},{"issue":"6","key":"doi240045r12","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.tips.2013.04.001","article-title":"The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities?","volume":"34","author":"Stahl","year":"2013","journal-title":"Trends Pharmacol Sci"},{"issue":"2","key":"doi240045r13","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","article-title":"Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.","volume":"14","author":"Finnerup","year":"2015","journal-title":"Lancet Neurol"},{"issue":"3","key":"doi240045r14","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.jaad.2016.02.1237","article-title":"Gabapentin and pregabalin for the treatment of chronic pruritus.","volume":"75","author":"Matsuda","year":"2016","journal-title":"J Am Acad Dermatol"},{"issue":"27","key":"doi240045r15","doi-asserted-by":"publisher","first-page":"4519","DOI":"10.1200\/JCO.2008.18.5017","article-title":"From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol.","volume":"26","author":"Colvin","year":"2008","journal-title":"J Clin Oncol"},{"issue":"1-2","key":"doi240045r16","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.pain.2004.12.010","article-title":"Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4).","volume":"114","author":"Bouhassira","year":"2005","journal-title":"Pain"},{"issue":"6","key":"doi240045r17","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1111\/j.1365-2133.2009.09347.x","article-title":"Quality of life evaluation in epidermolysis bullosa (EB) through the development of the QOLEB questionnaire: an EB-specific quality of life instrument.","volume":"161","author":"Frew","year":"2009","journal-title":"Br J Dermatol"},{"issue":"12","key":"doi240045r18","doi-asserted-by":"publisher","first-page":"7059","DOI":"10.3390\/ijerph19127059","article-title":"Transcultural validation of a Spanish version of the quality of life in epidermolysis bullosa questionnaire.","volume":"19","author":"Villar Hern\u00e1ndez","year":"2022","journal-title":"Int J Environ Res Public Health"},{"issue":"4","key":"doi240045r19","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.jaad.2013.04.053","article-title":"Measuring quality of life in epidermolysis bullosa in Mexico: cross-cultural validation of the Hispanic version of the Quality of Life in Epidermolysis Bullosa questionnaire.","volume":"69","author":"Frew","year":"2013","journal-title":"J Am Acad Dermatol"},{"issue":"2","key":"doi240045r20","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.ejpain.2007.05.003","article-title":"Pregabalin for relief of neuropathic pain associated with diabetic neuropathy: a randomized, double-blind study.","volume":"12","author":"T\u00f6lle","year":"2008","journal-title":"Eur J Pain"},{"issue":"1","key":"doi240045r21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40122-022-00451-4","article-title":"A Meta-analysis of randomized controlled trials comparing the efficacy and safety of pregabalin and gabapentin in the treatment of postherpetic neuralgia.","volume":"12","author":"Cao","year":"2023","journal-title":"Pain Ther"},{"issue":"4","key":"doi240045r22","doi-asserted-by":"publisher","first-page":"465","DOI":"10.18433\/J35K6N","article-title":"Role of pregabalin in management of pruritus: a literature review.","volume":"19","author":"Foroutan","year":"2016","journal-title":"J Pharm Pharm Sci"}],"container-title":["JAMA Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/articlepdf\/2825241\/jamadermatology_calvo_2024_oi_240045_1734108375.13548.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T16:01:12Z","timestamp":1734537672000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/fullarticle\/2825241"}},"subtitle":["A Randomized Crossover Trial"],"short-title":[],"issued":{"date-parts":[[2024,12,1]]},"references-count":22,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamadermatol.2024.3767","relation":{},"ISSN":["2168-6068"],"issn-type":[{"value":"2168-6068","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12,1]]}}}